We have been investigating the mechanisms of action of interleukin-6 (IL-6). The research focuses on the biochemical characterization of IL-6 receptors expressed in a panel of leukemic cell lines. In addition, we are involved in studies aiming at the elucidation of the signaling pathways mediated by IL-6. We have shown that iodinated IL-6 can interact with two distinct cell surface proteins (p80 and p110), which form the basis of the high-affinity IL-6 receptor on myeloma cells. Emphasis has been directed towards establishing with some degree of certainty whether p80 and p110 are proteins encoded by different genes. We have identified a human IL-6-responsive melanoma cell line (A375-C6), which expresses significant levels of the p110 but negligible levels of the p80 IL-6 receptor. In contrast to other melanoma cells, this cell line is completely growth-inhibited by IL-6. Attempts have been made to investigate IL-6-induced biochemical changes in this cell line. Preliminary studies showed that the antiproliferative effect of IL-6 in melanoma cells (A375-C6) is associated with the induction and enhanced secretion of fibronectin, tenascin, and other extracellular matrix proteins.